Project Summary/Abstract Pediatric brain cancer (gliomas) has a relative 5-year survival rate of below 30%, and represent the greatest cause of cancer-related deaths in pediatric patients. Current treatments such as chemotherapies, radiation, and/or surgery have limited success. Immunotherapy may be an ideal treatment option for these patients. Previously, we have created a form of immunotherapy, which consists of immune cells known as T cells. These T cells are engineered to express a chimeric antigen receptor (CAR) which has the ability to seek out and kill tumor cells. After testing this approach in the clinic, both safety and tumor killing need significant improvement. he specific In order to improve tumor killing, we propose here to target t environment surrounding a tumor. This environment is unique to the tumors themselves and do not exist within the rest of the patient body. Successfully targeting this environment will effectively decrease toxicity. To test this model, we will couple our environment-targeting T cell with a CAR designed to target tumor cells, thus increasing specificity. This project was carefully designed to provide a training opportunity to allow familiarization with the rapidly evolving field of cancer cell therapy and state of the art techniques to characterize tumor-specific T cells. The proposal and training will be performed at the state-of-the art research hospital, St. Jude Children?s Research Hospital. The results of this proposal could have immediate applications for cancer and could potentially lead to less toxicity than standard multimodal therapies such as chemotherapy or radiation.